1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
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High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures

  1. Kyaw Thu Minn
  2. Yuheng C Fu
  3. Shenghua He
  4. Sabine Dietmann
  5. Steven C George
  6. Mark A Anastasio
  7. Samantha A Morris  Is a corresponding author
  8. Lilianna Solnica-Krezel  Is a corresponding author
  1. Washington University in St Louis, United States
  2. Washington University School of Medicine, United States
  3. University of California, Davis, United States
  4. University of Illinois, Urbana-Champaign, United States
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Cite this article as: eLife 2020;9:e59445 doi: 10.7554/eLife.59445

Abstract

During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.

Article and author information

Author details

  1. Kyaw Thu Minn

    Department of Biomedical Engineering, Washington University in St Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  2. Yuheng C Fu

    Developmental Biology, and Genetics, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8037-6398
  3. Shenghua He

    Department of Computer Science & Engineering, Washington University in St Louis, St Louis, United States
    Competing interests
    No competing interests declared.
  4. Sabine Dietmann

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
  5. Steven C George

    Department of Biomedical Engineering, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  6. Mark A Anastasio

    Department of Bioengineering, University of Illinois, Urbana-Champaign, Urbana-Champaign, United States
    Competing interests
    No competing interests declared.
  7. Samantha A Morris

    Developmental Biology, and Genetics, Washington University School of Medicine, St Louis, United States
    For correspondence
    s.morris@wustl.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8561-4340
  8. Lilianna Solnica-Krezel

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    For correspondence
    solnical@wustl.edu
    Competing interests
    Lilianna Solnica-Krezel, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0983-221X

Funding

Children's Discovery Institute

  • Lilianna Solnica-Krezel

Washington University School of Medicine in St. Louis (Discretionary funds)

  • Lilianna Solnica-Krezel

Vallee Foundation (Vallee Scholar Award)

  • Samantha A Morris

Paul G. Allen Frontiers Group (Allen Distinguished Investigator Award)

  • Samantha A Morris

Alfred P. Sloan Foundation (Sloan Research Fellowship)

  • Samantha A Morris

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Anita Bhattacharyya, University of Wisconsin, Madison, United States

Publication history

  1. Received: May 28, 2020
  2. Accepted: November 17, 2020
  3. Accepted Manuscript published: November 18, 2020 (version 1)

Copyright

© 2020, Minn et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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